Nicotine: The Saint and the Devil

Nicotine: The Saint and The Devil

Nicotine is one of the many drugs that has a high dependence on the addiction and reliance of its users. Analogous to a countless number of drugs, the affects of Nicotine can both help to deteriorate and, surprisingly in this case, protect one’s health. Although the involvement of Nicotine with a myriad of illnesses that smoking tobacco and cigarettes usher, there is no denying its influence in the brain, specifically in the exclusive nicotinic receptors and reward system. Cigarette smoking still remains as the centerpiece of anti-drug agencies. With the dependence on the world-spread drug continuing steadily, researchers remain steadfast in their search for the positive and negatives effects on the brain that the drug entails.

The association of Nicotine with one of the larger leading causes of death validates its complexity and ability to stimulate the user’s mind. Research conducted by Dr. Paul Newhouse of Vanderbilt University’s Center for Cognitive Medicine sets out to prove that Nicotine has many beneficial aspects as well. Previous research already concludes that Nicotine is coupled with the area involved with acetylcholine, used for retention and cognitive intellect. Dr. Paul tested patients with Mild Cognitive Impairment (MCI), which is a common antecedent of Alzheimer’s Disease. Collecting data from 74 non-smoking adults that suffer from MCI, half were given Nicotine patches to be used daily and the other half placebo patches. After roughly half a calendar year, the data collected showed substantial increases in memory development and alertness with those that used the Nicotine patches. Perhaps one of the possibly surprising outcomes was the lack of withdrawal or dangerous side effects in the users. Nicotine can be safe drug, and is administered over the counter. Providing Nicotine treatment for disorders like schizophrenia, down syndrome, Alzheimer’s disease is a developing field, and it seems that the drug itself works at its highest capacity when there are already preexisting complications. It has often been assumed that people that suffer from health issues can self-prescribe his or herself with smoking to allow their mind to function properly. It is true that the population that suffers from Parkinson’s or Alzheimer’s is historically more dense with smokers. This leads one to wonder if said patients can attribute their addiction to this increase in capability or for other reasons like repeated reward. 

Many times, addiction is offset by a reward of some sort. If one is harming themselves during this process, it can be assumed that that reward is thought to be in his or her better interest moving forward. This Is due, in part, to the compensation factors that are associated with the drug. If heroin users didn’t experience a spontaneous stream of euphoria, the ability to refuse it should be much easier. In “Nicotine Potentiation of Excitatory Inputs to Ventral Tegmental Area Dopamine Neurons”, Dr. Dan McGehee tackles the exact areas that nicotine confronts in the brain. Subjecting a section of rat Vetral Tegmental Area (VTA) cells to the smoke of a cigarette, testing the response of neurons associated with neurotransmitter dopamine. Similar effects are seen in cocaine and other various amphetamine. Nicotine stimulates these reward-based neurons in the nucleus accumbens, rewarding the user with a rush much smaller in magnitude to that of heroine. Even so, the incredibly small euphoria of Nicotine may not play the largest role in the addiction though. Often times, the process and action of smoking coupled with the activities associated with it are what illicit this craving. A user can tell you first-hand of his or her routine of fetching their pack, going outside, taking their cigarette and finally receiving that mental break. Nicotine is a complex drug, and its ability to enhance the user for a long period of time with such little amounts makes it highly usable. As Dr. McGehee puts it, “It would be difficult to design a better drug to promote addiction”.

As research continues to be published on the many positive effects of Nicotine, it is only natural for one to question its part in the addiction to smoking. For those that already suffer from a shortcoming such as Parkinson’s, Alzheimer’s Disease, or Schizophrenia, it can work to improve long-lasting damage in memory and learning. What makes it highly dangerous is its ability to trigger the excitation of dopamine neurons, allowing the user to experience a low-grade rush long-lasting neurotransmitter effects. Even with the general decrease in cigarette smoking across the world, the several ways one can be drawn to Nicotine allows it to join an exclusive club of drugs that are done and abused almost in ubiquity. Depending on the user’s physical and mental state, Nicotine has a variety of neurological effects that seemingly ease the consumer’s mind. Even with its positive effects, the orchestrated release of dopamine, also in cocaine, can work against the mind in many ways in the long-term. Although the addiction of this infamous drug can be attributed to all of the affects above, there are many factors outside of the Nicotine itself that draw somebody back to their next dosage. Whether it is the desire for your next little rush or the longing for an allotment of time where your brain can function more properly, Nicotine provides the user with a luxury car with minimal gas.

Works Cited

"Dr. Paul Newhouse, Vanderbilt University – Nicotine and Memory." Dr. Paul Newhouse, Vanderbilt University – Nicotine and Memory. Web. 2 Mar. 2016.

Playing with snakes: A look at threat sensitivity and the fearless.

For most of us, the very sight of a snake would be enough to send us running but for some people touching them is as causal as petting a dog. In Time's article titled, How to Terrify the Fearless, neuroscience journalist Maia Szalavitz talks about Urbach-Withe disease, a genetic condition that renders those that it affects with what appears to be fearlessness. One patient diagnosed with the condition was not bothered by threatening animals like tarantulas and snakes. Her fearlessness even prevented her from being mugged once since her attacked was taken aback when she didn't respond to the fact that he had a knife to her throat. One speculation as to why this occurs is because the disease progressively destroys the amygdala which is considered the control center for most emotions including fear. In order to better understand this disease, researchers decided to look at things that would illicit fear in individuals with this disease. Researchers had participants of their study inhale carbon dioxide, the gas we would normally exhale. This created a feeling of suffocation that was terrifying for the individuals. This was for the most part the first time they had ever felt fear. This is interesting because it suggests that the amygdala is not solely responsible for fear. Instead it is primarily responsible for responding to potential threats from the outside world.

A different study, published by Dr. Stweart Shankman looked at exactly that, how threat sensitivity is involved in Panic Disorder. In his study, Dr. Shankman was interested in whether heightened sensitivity to threat was a possible mechanism of dysfunction in Panic Disorder. He tested this by having individuals with panic disorder partake in the NPU threat task. This task is divided into three portions, one in which the participants know they are safe from receiving a shock, one in which they are told they could possibly receive a shock when the image appears on the screen, and one in which they are told they could receive a shock at any time. The idea behind this was to determine whether predictable or unpredictable threats caused a heightened sensitivity to threat. The results determined that heightened sensitivity to both predictable and unpredictable threats were characteristics of individuals with Panic Disorder. The previous study supports this study in that those individuals responded to the predictable threat of carbon dioxide inhalation with panic.

References

1. Shankman, S. A., Nelson, B. D., Sarapas, C., Robison-Andrew, E. J., Campbell, M. L., Altman, S. E., Gorka, S. M. (2013). A psychophysiological investigation of threat and reward sensitivity in individuals with panic disorder and/or major depressive disorder. Journal of Abnormal Psychology, 122(2), 322-338.

2. Szalavitz, M. (2013, February 11). How to Terrify the Fearless | TIME.com. Retrieved from http://healthland.time.com/2013/02/11/how-to-terrify-the-fearless/

3. Charlie the Snake Charmer. Digital image. Izismile.com. N.p., 8 Sept. 2012. Web <http://img.izismile.com/img/img5/20120907/640/australian_toddler_is_a_real_snake_charmer_640_06.jpg>.

The Importance of Reading With a Keen Eye

TIME posted a very interesting article a few years ago relating to a recent increase in media attention to addictions. You can find the article here, and it is written by Maia Szalavitz. After hearing Dr. McGehee speak about nicotine-related mechanisms behind addiction forming, I was a little surprised at what I read in this article. By this, I mean I am surprised by how much the author undermined neuroscience research for addiction mechanisms.

Before we dive down and examine this article, it is important to keep two things in mind. First, this article was written in 2011. Although this time is still contemporary, less research about addiction was available to the author. Next, this article was written during a craze where “media headlines scream daily about new neuroscience findings…” on addictions. Some opinions could be exaggerated or biased towards whatever the mass’s opinion was (thank you, de Tocqueville).

This article starts off by claiming that “addictions hijack the brain’s pleasure systems” is circular reasoning and confuses the real purpose of the brain’s pleasure pathways. Szalavitz reasons that brain pathways are intended to make evolutionary activities (i.e., sex and eating) fun and enjoyable. Continuing, she states that drugs cannot be said to hijack the reward system to create addiction because that would also be to say that healthy urges like eating and sex would not cause addiction. To conclude her point, Szalavitz says sex and eating can become addictions by activating brain regions that generate pleasure from drugs, and that is why hijacking is not the appropriate description.

To be honest, Szalavitz’s logic can be pretty confusing. I almost agreed with her when it was stated that activities and substances cannot “hijack” a reward system because the system is meant to get us to pursue food and sex relentlessly. This made me think about what Dr. McGehee stated in his nicotine addiction findings. He stated during his presentation that the amount of cigarette packs a human smokes will plateau after 2-3 packs per day. The body can form needs and desires for a drug, but with some substances the body can also say “enough is enough.” I believe the same idea works for food too. I cannot pursue Chipotle endlessly. I will undoubtedly become sick of it after 1.5-2.0 burritos and not want to see food for a good half day. I believe Szalavitz needs to be more careful with saying that we endlessly pursue sex and food. A tribal and sensory-driven view of humanity undermines our agency and ability to reject certain sensations.

Lastly, Szalavitz states that “no study has ever isolated a simple brain change that is always seen in addicts and never in non-addicts. And although some studies have found changes that can predict an addict’s odds of relapse, they’re not always accurate.” I would like to note here how the first sentence in Dr. McGehee’s paper, from 2011, titled “Nicotine Potentiation of Excitatory Inputs to Ventral Tegmental Area Dopamine Neurons” began. It states, “Drug-induced changes in synaptic strength are hypothesized to contribute to appetitive behavior and addiction.” This shows first that Szalavitz may not have been quite up to date with neuroscience literature before writing this article. Secondly, Szalavitz assumes that addiction is a black-and-white mechanistic process. Continuing with Dr. McGehee’s study, there are varying levels of smokers. Accordingly, the long-term potentiation in Ventral Tegmental Area dopamine neurons may also vary with the level of addiction (i.e., a process hypothesized to underlie nicotine addiction can vary with level of addiction). Assuming that a process will either be present or absent depending on addiction undermines the complexity of understanding addiction circuits.

To conclude, it is always important to read news articles with a critical eye. In this case, hearing that no study has been conducted to isolate a simple change in addict’s or non-addict’s brains is true, but very misleading. The fact of the matter is that addiction is much more complex than one change. Understanding the summation of many changes in neural networks will ultimately be a key to understanding addiction and to help us better treat it. 

Smell your way to a cure

In our daily lives, we come across millions of sensory stimuli that we don’t have to actively think about to interpret. But since when did our reactions to these stimuli become so automatic or instinctive? What makes one person despise the smell of cheese but one person love the smell? These questions, and many like them, will hopefully be fully answered in the future, but as a starting point, Dr. Timothy Bozza has researched an extensive amount, especially in regards to the function and significance of the TAAR receptors in the olfactory system. His research has examined two main potential functions: 1. TAARs being used as high affinity amine receptors (maybe even the most sensitive of the olfactory receptors for detecting amines) 2. TAARs potentially working with the very circuits that drive innate behaviors such as with the aversive behavior mice have towards PEA.

First, to figure out if the TAARs are the receptors with the highest affinity towards amines, Dr. bozza and his research team used TAAR cluster deletion through in vivo transallelic recombination to create a deletion allele that would in turn get rid of the TAAR cluster. Through this deletion method, the team would be able to determine a potential function of the TAARs based on what functions were lesser in function after the deletion. And the results did not disappoint. As hypothesized, Dr. Bozza was able to see that after the deletion of the TAAR cluster, the high sensitivity amine responses were gone because the glomeruli were not active. However, because the research team was unable to view the all parts of the glomeruli, concrete conclusions were unable to be made about this hypothesis.

Thus, Dr. Bozza and his research team developed an experimental method that could generate more concrete conclusions for the first hypothesis. They used an odor detection device to ask the mice if they smelled the odor or not. With the elimination of the TAAR cluster, they saw a 50 fold decrease in the sensitivity towards phenylethylamine and while with the wild type as the concentration of the odor increased, the performance also increased, the experimental group with the deleted TAARs needed an even higher concentration to match the performance of the wild type. Isopentylamine was also examined and showed similar results in that the mice with the deleted TAARs were less sensitive towards the isopentylamine. Thus, from this study, Dr. Bozza and his research team was able to confirm that TAARs are key to determining the detection thresholds for amines.

Following, Dr. Bozza also looked at how the deletion of a single TAAR would affect the detection threshold. The team deleted TAAR4 and from this they saw a decrease in the response to phenylethylamine in the dorsal bulb which is similar to the result they saw in the aforementioned experiment. Thus, from this study, they were able to conclude that for a single receptor can indeed have a significant impact on the detection of a single odor like in the case of PEA.

Next, Dr. Bozza and his team designed studies to test out the second hypothesis which relates TAARs to circuits that drive innate behaviors. Here, the focused on PEA which is a TAAR4 ligand that is present in carnivore/predator urine. They chose PEA specifically because mice have an innate aversive response to PEA. A place preference assay where in one chamber, there was odor and in one there was water, was done where the preference index was evaluated. From the deletion of the TAAR cluster, PEA was no longer aversive and this result was seen in IPA, NMP, CAD, and the natural stimulus Puma as well. Thus, the study revealed that the deletion of all TAARs stops the aversion towards amines.

Furthermore, Dr. Bozza and his team also examined the effects of deleting just the TAAR4 and from this study, they were able to conclude that the deletion of TAAR4 causes the abolishing of aversion for specific amines such as PEA and predator urines. For the other amines, the aversion remained for the most part. Therefore, looking at the grand scheme, the team was able to infer that the deletion of a single TAAR gene could influence different odor guided behaviors. From just these the studies conducted by Dr. Bozza, it is clear that the olfactory system has a great influence on much of our body responses and behaviors, thus, to expand a bit from this idea, we can examine an interesting find on the influence of olfactory receptors on a potential treatment option for patients suffering from Leukemia.

In research study conducted by Professor Hanns Hatt from the Ruhr-Universität Bochum, it was demonstrated that olfactory receptors were not only present in the nose but also in “white blood cells in humans” (Olfactory receptors in the blood). The research team were able to specify which olfactory receptor was involved with the white blood cells and it turned out to be the OR2AT4 receptor. This receptor was found to be activated by Sandalore which is not a natural but an odorant synthetically developed with a sandalwood odor. Through the activation of the O42AT4 receptor, researchers found that it caused a halt to the growth of leukemia cell growth as well as the death of the leukemia cells as well. Thus, because of this shrinking value in leukemia cell growth, the researchers were able to see an increased in the red blood cell count, a positive for patients affected with Leukemia.

For the specifics on the signaling pathways regarding the OR2AT4 receptor, we can look at the model relationship of the nose and its olfactory cells. Through the activation of the OR2AT5 receptor by Sandalore, the calcium ion concentration in the human blood cells will increase which will then activate signaling pathways. These signaling pathways will cause the phosphorylation of specific enzymes, specifically the MAP kinases and the process moves on from there with regulation. (Olfactory receptors in the blood)So far, there have been seven olfactory receptors in the blood cells that have been found, Professor Hatt and the research team are continuously working to untangle the mystery behind the relationship between the olfactory receptors and the cell, for example, currently, they are looking at another receptor that is activated by isononyl alcohol. Thus, while the exact details on the potential for the OR2AT4 receptor to help with treatment of Leukemia have not been all worked out, the fact that there is this potential for a much-needed treatment option is a sign we are headed in the right direction. 

Works Cited

 Figure 3: Sandalore Increases the Intracellular Ca2+ in the White Blood Cells of AML Patients. Digital image. Nature.com. Nature Publishing Group, 25 Jan. 2016. Web. 4 Mar. 2016. <http://www.nature.com/articles/cddiscovery201570/figures/3>.

Pacifico et al., An Olfactory Subsystem that Mediates High-Sensitivity Detection of Volatile Amines, Cell Reports (2012), http://dx.doi.org/10.1016/j.celrep.2012.06.006

"Olfactory Receptors in the Blood." EurekAlert! American Association for the Advancement of Science, 1 Feb. 2016. Web. 05 Mar. 2016. < http://www.eurekalert.org/pub_releases/2016-02/rb-ori020116.php>.

 

Criminal Minds

More and more in the news we hear about senseless acts committed by serial killers and murderers. And we ask ourselves, how can a human being even think about doing something so evil and harmful to another human being? We question the intentions of these killers and try to figure out what is going on inside their heads that could trigger such violent actions. Sadly, most of the time we aren’t able to question their intentions because most of these troubled individuals end up committing suicide.

During the first couple weeks of Neuroscience Seminar, we had Brian Sweis come in and talk about research centering around the orbitofrontal cortex (OFC).  He explains how humans with damage in this region do not experience regret and how fMRI tests have shown functional activity in the OFC region during regret. However in nonhuman primates, specifically rats, we are not sure if they are even mentally capable of experiencing regret. A decision making task called Restaurant Row was constructed where the rats were put in a series of take or skip choices involving food. The data suggested that the OFC is indeed vital for representing outcomes when animals think about past decisions. In the end, we know that rats experience regret but we are still not clear if the orbitofrontal cortex is necessary for the emotion of regret. However, there is evidence that the orbitofrontal cortex is active and necessary for experiencing regret in humans and damage to it results in no showing of regret and anticipation of negative consequences. This led me to question if we can further our research and perhaps find a connection between brains of serial killers and orbitofrontal cortex damage. The orbitofrontal cortex, in my opinion, could be the reason for the creation of serial killers and murderers when damaged. 

An article I read called “How to spot a murderer’s brain” talks about the brain patterns found between the minds of murderers.  Adrian Raine is a scientist who has done extensive research on the brains of serial killers. Like other scientist, he too has noticed a distinct difference between the brains of normal people and serial killers. The difference was found in the OFC or lack thereof. The OFC of serial killers was significantly smaller or nonexistent. From the article, I learned that deficiency in the OFC not only caused no feeling of regret but other behaviors such as less control over the anger, an increased addiction to risk, a loss of self-control, and poor problem solving skills. The article changed my view on finding the definitive factor that makes up a killer, which I thought would be damage to the OFC after hearing Brian Sweis’ findings. Yes, damage or less activity in the orbitofrontal cortex can be indicative of a serial killer, but there are several other factors other than biological similarities that fall into the equation like poverty, bad neighborhoods, and poor education. Adrian Raine, the scientist who was conducting the research, did a brain scan on himself and found similarities of that of the brain of a killer. But you can see he turned out to be fine. In the end, it goes back to the classic nature versus nurture debate. We won’t be able to confirm what exactly brings forth the upcoming of a killer. There are so many variables involved and really it matters how our biological makeup reacts with the environment we live in.

                                                                       Works Cited

Adams, Tim. "How to Spot a Murderer's Brain." The Guardian. Guardian News and Media, 11 May 2013. Web. 05 Mar. 2016.

Steiner, Adam P., and A. David Redish. "Behavioral and Neurophysiological Correlates of Regret in Rat Decision-making on a Neuroeconomic Task." Nature Neuroscience Nat Neurosci 17.7 (2014): 995-1002. Web.